Year : 2015 | Volume
: 40 | Issue : 3 | Page : 148--149
Factor XIII deficiency: the first case reported from Nepal
Bishesh S Poudyal1, Gentle S Shrestha2,
1 Department of Internal Medicine, Civil Service Hospital, Kathmandu, Nepal
2 Department of Anaesthesiology, Institute of Medicine, Tribhuvan University Teaching Hospital, Kathmandu, Nepal
Gentle S Shrestha
Department of Anaesthesiology, Institute of Medicine, Tribhuvan University Teaching Hospital, Maharajgunj, Kathmandu
The initial hemostatic plug is not sufficient to prevent blood loss unless it is stabilized by the action of plasma factor XIII. Congenital or acquired factor XIII deficiency must be considered when a patient has a major bleeding disorder and all of the initial screening laboratory tests are normal, including prothrombin time, activated partial thromboplastin time, platelet count, and bleeding time. Here we report the case of a child with congenital factor XIII deficiency, who presented with bleeding from umbilical stump and spontaneous hematoma in the left buttock.
|How to cite this article:|
Poudyal BS, Shrestha GS. Factor XIII deficiency: the first case reported from Nepal.Egypt J Haematol 2015;40:148-149
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Poudyal BS, Shrestha GS. Factor XIII deficiency: the first case reported from Nepal. Egypt J Haematol [serial online] 2015 [cited 2020 Mar 28 ];40:148-149
Available from: http://www.ehj.eg.net/text.asp?2015/40/3/148/164742
In 1944, Robins  postulated that a deficiency of fibrin stabilizing factor, which was later known as factor XIII, would produce a serious bleeding disorder. During the last four decades, over 200 cases of congenital factor XIII deficiency have been reported in the literature  . It is estimated that about one in every one to five million people has factor XIII deficiency. The disorder is inherited as an autosomal recessive trait  .
A 16-month-old male child was referred to the Hematology Unit for evaluation of hematoma in the left buttock. There was no history of trauma. His bleeding history dated back from his infancy, when he bled significantly from the umbilical stump. There was a history of large superficial ecchymoses in different parts of the body at different times. The patient also had a history of prolonged bleeding and minor injuries. He did not have any siblings, and a family history of bleeding disorder was absent. Physical examination revealed ecchymosis on the right upper arm and lower back. Tender, swollen, hot, hard, mobile indurated hematoma was found on the left buttock. It measured 4 × 4 cm in size. Pallor was absent. Lymph nodes were not palpable, and there was no organomegaly.
Suspecting bleeding disorder, prothrombin time, activated partial thromboplastin time, bleeding time, thrombin time, and platelet count were investigated. All these laboratory tests were within normal limits. As the patient had the unique history of bleeding from healthy umbilical cord, clot solubility functional test was performed. The clot dissolved in 25 min, which is suggestive of factor XIII deficiency. Mixing study was performed, and it ruled out the possibility of acquired factor XIII deficiency. Thus, the patient was diagnosed to have congenital factor XIII deficiency.
The patient was transfused 150 ml of fresh frozen plasma. His symptoms resolved and was discharged home.
Congenital factor XIII deficiency is a rare bleeding disorder, with a frequency of one in 2 000 000 in general population  . Clinically affected patients typically have plasma factor XIII level less than 1% of normal, and the bleeding is attributed to accelerated fibrin clot degradation  . Bleeding phenotype in patients with inherited factor XIII deficiency is unusually severe. Abnormal bleeding manifests shortly after birth, when bleeding from the healthy umbilical cord remanant occurs. This has been a prominent feature, reported in up to 80% of cases  . Umbilical stump bleeding is an uncommon presentation for other congenital bleeding disorders. Our patient had a history of umbilical stump bleed. Other bleeding manifestations include soft tissue hemorrhage, hemoarthrosis, hematomas, and development of large pseudocysts. Our patient had a history of repeated hematomas and ecchymosis. Intracranial hemorrhage is more prevalent in factor XIII deficiency than in other inherited bleeding disorder  . Male and female infertility has also been reported with factor XIII deficiency. The manifestations of factor XIII deficiency vary greatly among patients and may not necessarily present as bleeding symptoms.
Acquired factor XIII deficiency can be ruled out in suspected patients by performing the mixing study. Acquired factor XIII deficiency is reported in patients taking isoniazid, phenytoin, procainamide, penicillin, and valproic acid. It also occurs in association with autoimmune diseases, in patients with monoclonal gammopathy, or it may be idiopathic  . We ruled out all the possibilities of acquired factor XIII deficiency by detail history taking and investigation.
The prothrombin time, activated partial thromboplastin time, bleeding time, thrombin time, and platelet count are normal in factor XIII deficiency. The clot solubility test in 5 mol/l urea is the most useful screening test for factor XIII deficiency. In these conditions, clots formed in the absence of factor XIII activity dissolve within 60 min. In contrast, normal clots covalently modified by factor XIIIa remain insoluble for at least 24 h  . In our case, clot dissolved within 30 min.
Patients are usually treated with factor XIII concentrate. Alternative treatment options are fresh frozen plasma and cryoprecipitate. Our patient was treated with fresh frozen plasma, as factor XIII concentrate is not available in Nepal. Plasma levels of factor XIII as low as 2-3 IU/dl are adequate for normal hemostasis. However, for patients with major trauma, or those undergoing surgery, a higher level of factor XIII (25-50%) is required.
Factor XIII deficiency is a very rare disorder that can present with severe and life-threatening bleeding. It should be considered when routine screening tests of coagulation are within normal limits. Factor replacement, fresh frozen plasma, or cryoprecipitate is indicated for treatment of bleeding or during surgery.
Conflicts of interest
There are no conflicts of interest.
|1||Robbins KC. A study on the conversion of fibrinogen to fibrin. Am J Physiol 1944; 142:581-588.|
|2||Loewy AG, McDonagh J, Mikkola H, Teller DC, Yee VC. Structure and function of factor XIII. In: Colmam RW, Hirsh J, Marder VJ, Clowes AW, George JN eds. Hemostatis and thrombosis: basic principles and practice. Philadelphia, PA: Lippincott Williams and Wilkins; 2001. 233-247.|
|3||Bolton-Maggs PHB, Perry DJ, Chalmers EA, Parapia LA, Wilde JT, Williams MD, et al. The rare coagulation disorder - review with guidelines for management from the United Kingdom Haemophilia Centre doctor's organization. Haemophilia 2004; 10 :593-628.|
|4||Board PG, Losowsky MS, Miloszewski KJ. Factor XIII: inherited and acquired deficiency. Blood Rev 1993; 7 :229-242.|
|5||Greenberg CS, Sane DC, Lai TS. Factor XIII and fibrin stabilization. In: Colmam RW, Hirsh J, Marder VJ, George JN eds. Hemostatis and thrombosis: basic principles and practice. Philadelphia, PA: Lippincott Williams and Wilkins; 2006. 317-334.|
|6||Kitchens CS, Newcomb TF. Factor XIII. Medicine (Balt) 1979; 58 :414-429.|
|7||Duckert F. Documentation of the plasma factor XIII deficiency in man. Ann N Y Acad Sci 1972; 202:190-199.|